The research will document the role of the genotype in the cardiovascular and metabolic responses to aerobic exercise-training and the contribution of inherited factors in the changes brought about by regular exercise for several cardiovascular disease and diabetes risk factors. A consortium of 5 laboratories from 5 different institutions in the US and Canada will be involved in carrying out this study. A total of 650 sedentary subjects will be recruited, initially tested, exercise-trained in the laboratory with the same program for 20 weeks, and re-tested. These subjects will come from 90 families of Caucasian descent with both parents and three biological adult offsprings and 40 families of African-American ancestry. Oxygen uptake, expiratory volume and respiratory exchange ratio, blood pressure, heart rate, blood lactate, glucose, glycerol and free-fatty acids, stroke volume and cardiac output will be measured during exercise before and after training and maximal oxygen uptake will be determined. Plasma lipids, lipoproteins and apoproteins, glucose tolerance and insulin response to an intravenous glucose load, plasma sex steroids and glucocorticoids, resting systolic and diastolic blood pressures, and body fat and regional fat distribution will also be assessed. Dietary habits, level of habitual physical activity and other lifestyle components will be assessed by questionnaires. Genetic analyses will include the determination of the heritability level for each phenotype and its response to regular exercise, testing for the presence of paternal or maternal effects, sex-limited effects, major gene effects and segregation patterns. Multivariate genetic analyses and complex segregation analyses will be used to develop hypotheses concerning the genetic basis of the response to exercise-training. This research should increase our understanding of human variation, the genetics of adaptation to exercise-training and of the concomitant changes in cardiovascular disease and diabetes risk factors.